The present invention relates generally to the first efficient process for the manufacture of cyclic cis-vicinal tertiary diamines, compounds known to be extremely effective as drugs as well as possible catalysts for certain organometallic reactions.
Polyamines, including vicinal diamines, play a critical role in metabolism, controlling cell growth and cell division. The polyamines spermine and spermidine complex with DNA, RNA and t-RNA changing the conformations of these host molecules. Among diamines not found in living organisms, some are antineoplastic, for example 1,2 bis(N-3,5-diketopiperazenyl)propane, whereas others are metastatic, bacteriacidyl or act as neurotoxins.
The most potent agent against testicular cancer is a platinum complex of cis-1,2-diaminocyclohexane. The effectiveness of this drug is believed to result from the cis arrangement of the amino groups.
Vicinal tertiary diamines accelerate the reactions of organolithium compounds, compared to just using monoamines.
Vicinal diamines exert significant chemotherapeutic effects and are often active as catalysts in simple organic reactions. The pharmacological and catalytic potential of these substances is significantly enhanced when the amino groups are oriented cis to one another.
Such compounds have not been extensively used in medicine because hitherto there has been no efficient method to make them. With the present invention it is now possible to efficiently synthesize cyclic cis-vicinal tertiary diamines.
Existing methods for synthesizing vicinal tertiary diamines are inefficient; most methods are not stereospecific and are unsuitable to be scaled up for commercial production. These existing methods include use of Curtius reactions, azide chemistry, metalloamination, imidoalkyl osmium and tosylimino selenium, reagents, respectively, and reductions of bis vicinal-nitro compounds, oximes, nitroso compounds and nitrile oxides. Another method based on cyanamino bromination of alkenes has been used to produce unsubstituted cis vicinal diamines. Recently a method which has had some success is the preparation of vicinal tertiary diamines via reductive animation of a 2-dialkylamino cyclic ketone.
So far applicants can determine, however, there are no prior art references or practices which comprises the catalytic reduction of cyclic aminoenamines to efficiently synthesize cyclic cis-vicinal tertiary diamines. The present invention therefore provides an improved method of synthesizing cyclic cis-vicinal tertiary diamines.